This proposal describes a population-based study to examine the relation of blood levels of perfluroalkyl chemicals (PFCs) to the presence of chronic kidney disease (CKD) and cardiovascular disease (CVD) in two separate studies in a population-based sample of Appalachian adults. We are requesting funding for secondary analysis of data. This proposal takes advantage of the data on exposures and outcomes already gathered on a population-based cross-sectional sample of 56,554 Appalachian adults who were aged e18 years and 53% of whom were women, residing in six communities in Ohio and West Virginia, called the C8 Health Study. In the study, we have data available on serum PFC levels, the main exposure of interest, on all members of the cohort, including serum levels of perfluorooctane sulfonate (PFOS or C8s), perfluorooctanoic acid (PFOA or C8), perfluorohexane sulfonate (PFHxS or C6S), perfluorohexanoic acid (PFHxA or C6), perfluoropentanoic acid (PFPeA or C5), perfluoroheptanoic acid (PFHpA or C7), perfluorononaoic acid (PFNA or C9), perfluorodecanoic acid (PFDA or C10), perfluoroundecanoic acid (PFUnA or C11), and perfluorododecanoic acid (PFDoA or C12) as part of a previous court-mandated health survey. We also have available pertinent data that will enable us to define CKD and CVD, the main outcomes of interest. This includes serum creatinine measurement that is available on all study subjects, enabling us to estimate glomerular filtration rate (eGFR), estimated by the Modification of Diet in Renal Disease (MDRD) equation. We will define CKD as an eGFR of <60 mL/min per 1.73 meter2, consistent with current guidelines. We also have data on validated, physician diagnosed CVD, including coronary heart disease and stroke. We will examine the putative association between serum PFCs and the outcomes of interest (CKD or CVD) employing standard epidemiological techniques, including multivariable logistic regression models adjusting for age, gender, race- ethnicity, education, body mass index, and other confounders. Our study provides a unique and cost-effective opportunity to assess the independent association between serum PFC and the presence of CVD and CKD in a large community-based cohort in Appalachia, which is a designated health disparity population. Data from our study will improve the understanding of the health effects of PFCs on humans. Results from the current study will also guide the planning of future follow-up studies of the same cohort population. PUBLIC HEALTH RELEVANCE: Perfluroalkyl chemicals (PFC) are detectable in the blood of >98% of S adults. We will study the association between blood PFCs and kidney disease and cardiovascular disease. If we find an association, it indirectly suggests that reducing PFCs may have a role in preventing these diseases.